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Theranostics: A New Holistic Approach in Nanomedicine
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
Ankit Rochani, Sreejith Raveendran
Most bioconjugation concepts depend on technologies like fluorescence resonance energy transfer or froster resonance energy transfer (FRET), fluorescence correlation spectroscopy (FCS), or Fluorescence fluctuation spectroscopy (FFS). Lucas et al. developed polymeric pegylated poly[2-(dimethylamino) ethyl] methacrylate-co-aminoethyl methacrylate ((PEG-PDMAEMA-co-AEMA))-Cy5-labeled poly(l-Lysine) and rhodamine-labeled-ON complex. They used FFS for tracking the nanocomposite in cell lines [23]. Due to the high resolution of FFS, they were able to map the dissociation of the polymeric part from labeled-ON within the cytoplasm. Bioconjugational chemistry is an important tool for synthesis of novel materials that can be used for developing TNPs for advanced drug delivery applications [24–27]. Fluorescence imaging (a type of photoluminescence (PL) imaging) has been used to develop image-guided surgeries and other medicinal applications. These conjugation techniques and PL imaging methods are the basic principle behind the development of more complex and advanced NP-based theranostic systems. The classical conjugation chemistry works better with molecules with free proton-donating and proton-accepting moieties to create covalent conjugation. However, the conjugation between fluorescing drug molecules and polymeric biomaterials (protein, ON, or polymers) can be difficult to execute in certain cases. Hence, self-assembled particles can come in handy in these situations to create theranostic or imaging particles.
Virus-Based Nanocarriers for Targeted Drug Delivery
Published in Devarajan Thangadurai, Saher Islam, Charles Oluwaseun Adetunji, Viral and Antiviral Nanomaterials, 2022
Semra Akgönüllü, Monireh Bakhshpour, Yeşeren Saylan, Adil Denizli
Functionalization is reached via attracting the peptides, antibodies, oligonucleotides, fluorescent reagents, drug molecules, and proteins to the capsid through various chemical materials, including maleimide, N-hydroxy-succinimidyl ester, carbodiimide, and isothiocyanate. Genetically, a cysteine residue could be let into a subunit that shows a thiol-based group in the assembled surface capsid structure (Wang et al. 2002). The summary of the general bioconjugation techniques used for modification is shown in Figure 9.5 (Alemzadeh et al. 2018). A new way to conduct bioconjugation is through click-chemistry. Magnificent progress in the chemoselective ligation on the surfaces of the virus utilised click-chemistry where the virus-based nanocarriers could be coupled in an orthogonal style without using safety groups. The click-chemistry reaction is chosen for bioconjugation because is quicker, bio-orthogonal, and more easily continues than suitable NHS reactions. The other chemo-selective approach is hydrazone-ligation. All chemical materials in the drug would be immediately bioconjugated to the surface of the virus, which is very important (Pokorski and Steinmetz 2011).
Chimeric VLPs
Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
Pokorski et al. (2011b) ensured the cell targeting with the Qβ VLPs displaying epidermal growth factor (EGF). The latter was fused C-terminally to the Qβ coat. The co-assembly of the wild-type Qβ and EGF-modified subunits resulted in the structurally homogeneous nanoparticles displaying between 5−12 copies of EGF on their exterior surface. The particles were found to be amenable to bioconjugation by standard methods as well as the high-fidelity CuAAC reaction. Remarkably, such chemical derivatization did not impair the ability of the particles to specifically interact with the EGF receptor. In addition, the particle-displayed EGF remained biologically active when promoting autophosphorylation of the EGF receptor and apoptosis of A431 cells. Therefore, the mosaic Qβ-EGF VLPs were proposed as useful vehicles for the targeted delivery of imaging and/or therapeutic agents.
An overview of process development for antibody-drug conjugates produced by chemical conjugation technology
Published in Expert Opinion on Biological Therapy, 2021
Yutaka Matsuda, Brian A. Mendelsohn
The development of conjugation methodology is a popular topic of interest in the oncology field. A number of review manuscripts have been published on this continuously evolving technology [43–45]. To date, all FDA-approved ADCs are produced by conjugation to either the amino groups of solvent-exposed lysines or thiol groups of cysteines revealed by disulfide reduction of interchain disulfides. The drug-antibody ratio (DAR) of the resulting ADC is known to have a significant impact on its drug efficacy and safety profile [46]. Typically, high DAR species may not only lead to ADC aggregation, but also can show fast clearance in vivo, potentially resulting in reduced safety and drug efficacy [47,48]. Lower DAR species may present problems related to drug efficacy as naked antibody (or lightly loaded species) may compete for limited target antigens; depending on the drug efficacy of the payload itself, the optimal DAR of the ADC will vary and the ability to control for the optimal DAR is required for ADC manufacturing [49]. It is also known that the stability of the linker depends on the position of the conjugation site on the antibody, indicating that the conjugation position can affect the stability and pharmacokinetics of ADCs [50,51]. With the goal of producing optimal ADC formats displaying enhanced clinically relevant TIs, wide-ranging research exploring well-controlled conjugation methods is enthusiastically ongoing in the bioconjugation industry.
Potent activity of bioconjugated peptide and selenium nanoparticles against colorectal adenocarcinoma cells
Published in Drug Development and Industrial Pharmacy, 2019
V. R. Ranjitha, Umashankar Muddegowda, V. Ravishankar Rai
In recent times, there has been increasing in interest in the construction of new materials by the combination of both natural and synthetic molecule which basically opens up a new era for the bioconjugation [1,2]. On the other hand, bioconjugation simply means the process of linking two molecules together thus creating a new complex having the combined properties of each constituent [3]. The molecules used for the bioconjugation includes DNA, proteins, short chain peptides, drugs, fluorescent dyes, ligands, synthetic polymers, and the list goes on based on the application to which it is used [4]. Within this group, peptide specifically short chain peptides offer several advantages because of low cost, simplicity, biocompatibility, and its ready availability of the functional groups that lead to the effective bioconjugation with any biological moiety [5,6]. Meanwhile, short chain synthetic peptides are proven to be an excellent protein mimicking molecule and binding to the functional sites of the protein fragments. Such synthetic peptides can produce exact copies of protein fragments resulting in chemical modifications and proteolytic stability of the molecules [7,8].
Therapeutic biomaterials based on extracellular vesicles: classification of bio-engineering and mimetic preparation routes
Published in Journal of Extracellular Vesicles, 2018
Pablo García-Manrique, María Matos, Gemma Gutiérrez, Carmen Pazos, María Carmen Blanco-López
Functionalization of liposomes with biomolecules is possible, owing to the different headgroup-modified lipids that are available [97]. Headgroup modification usually includes a molecule of polyethylene glycol as a spacer between the functional group and the polar region of the lipid. This avoids the sterical hindrance caused by the proximity of biomolecules and liposome surface. The chemical modification includes the introduction of different types of functional groups, such as biotin, amine, maleimide, carboxylic acid, folate, cyanur, DBCO, azide and succinyl groups. These groups determine the crosslinking strategy [98–101] which should not compromise the biological function. Bioconjugation should ideally be carried out under mild conditions, aqueous media and chemoselectivity, and with a high yield.